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Schuch JB, Genro JP, Bastos CR, Ghisleni G, Tovo-Rodrigues L,

Schuch JB, Genro JP, Bastos CR, Ghisleni G, Tovo-Rodrigues L,

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American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2017 09 13() doi 10.1002/ajmg.b.32599Abstract
The circadian clock system drives daily rhythms in physiology, metabolism, and behavior in mammals. Molecular mechanisms of this system consist of multiple clock genes, with Circadian Locomotor Output Cycles Kaput (CLOCK) as a core member that plays an important role in a wide range of behaviors. Alterations in the CLOCK gene are associated with common psychiatric disorders as well as with circadian disturbances comorbidities. This review addresses animal, molecular, and genetic studies evaluating the role of the CLOCK gene on many psychiatric conditions, namely autism spectrum disorder, schizophrenia, attention-deficit/hyperactivity disorder, major depressive disorder, bipolar disorder, anxiety disorder, and substance use disorder. Many animal experiments focusing on the effects of the Clock gene in behavior related to psychiatric conditions have shown consistent biological plausibility and promising findings. In humans, genetic and gene expression studies regarding disorder susceptibility, sleep disturbances related comorbidities, and response to pharmacological treatment, in general, are in agreement with animal studies. However, the number of controversial results is high. Literature suggests that the CLOCK gene exerts important influence on these conditions, and influences the susceptibility to phenotypes of psychiatric disorders.